Osteosarcoma: Our study with newly diagnosed localized and metastatic osteosarcoma (OS), in collaboration with several other centers was concluded in almost 2 years ago, and patients are continued to be followed. We will likely report the findings within the next 2 years with sufficient follow-up. The companion study evaluating the value of dynamic MRI imaging (DEMRI) is predicting response to neoadjuvant chemotherapy evaluated approximately 22 patients studied at the NCI and was insufficient to reach any conclusions unfortunately based on the small sample size. The high-dose chemotherapy with autologous stem cell rescue arm of this study did not improve DFS by greater than 50% in poor risk patients. A multi-institutional study to evaluate an Astra-Zeneca src-kinase inhibitor in pulmonary metastatic osteosarcoma is now approved and should open for accrual within the next 2 months. We performed preclinical testing in our osteosarcoma models and demonstrated that the drug inhibits targets of src and also showed that human osteosarcoma tumors express high levels of activated src. The study will randomize patients who present with pulmonary metastases to receive standard resection of pulmonary nodules vs. surgery plus treatment with the kinase inhibitor to determine whether DFS can be prolonged with treatment. The study will be performed through a new sarcoma treatment consortium called SARC and all agreements between SARC and AstraZeneca are now in place. We also completed accrual to the osteosarcoma cohort in a SARC Phase II study using a human monoclonal antibody to the IGFIR in recurrent osteosarcoma. Thirty-five patients from around the U.S. were entered, and data are currently being analyzed. Ewings Sarcoma: Our new salvage therapy for recurrent osteosarcoma and Ewings sarcoma using a combination of sequential gemcitabine/docetaxel based on preliminary in vitro synergy and previous activity of the single agents was also tested through the SARC consortium. The osteosarcoma cohort was fully accrued and terminated due to inactivity. The Ewings cohort is not fully accrued, but unfortunately we have had no accruals in the past year, and we are seriously considering whether or not we should terminate the study. Accruals have been significantly impacted by the opening of our IGFIR Ab study for Ewings sarcoma (see below). We recently opened an international study using a human monoclonal antibody directed against the IGFI receptor in Ewings, rhabdomyosarcoma, osteosarcoma, synovial sarcoma and several other rare adult type sarcomas through the SARC clinical trials consortium. I serve as the chairman of the study committee and played a major role writing the protocol. The study opened in December 2007 and has accrued over 175 patients to date, including 60 patients with Ewings sarcoma. Since there were responses seen in Ewings sarcoma in several Phase I studies using monoclonal Ab to the IGFIR, this cohort has been of particular interest, and we continue to see responses in the Phase II study. The osteosarcoma cohort is fully accrued and analysis is onging, while the other cohorts are continuing to accrue. We also have recently opened a companion biology study to try to identify biomarkers that might predict response to this targeted therapy. Based on the encouraging results in Ewings sarcoma with this antibody treatment, we have recently written a randomized study comparing standard salvage therapy for Ewings sarcoma, cytoxan plus topotecan, to the same chemotherapy regimen plus the IGFIR Ab. It is hoped that this study will serve as a registration study if the results show an improvement of progression-free survival in the arm that includes the IGFIR Ab. I will again serve as the protocol study chairman for this study that we hope to have open by late spring 2009. Of significant note is that based on the results of the pediatric Phase I study using the same Ab that was chaired by Dr. Frank Balis in the Pediatric Oncology Branch, we will be allowed to accrue patients from ages 2 to 75 on this proposed study. We continue to accrue patients to a study evaluating treatment of MPNST patients, in both the sporadic and NF-1 associated setting. We will evaluate the objective response rate of alternating Ifos/etoposide with Adria/Ifos in these patients, followed by surgical resection after 4 cycles of therapy. We have now entered 8 patients to date, and this study is now accruing patients across the SARC Consortium.